Fluids/Electrolytes/Acid/Base Flashcards

Question

Effective vs Ineffective osmoles | Examples of each How do they affect water movement?

Answer 1

**Effective:** Do not freely cross cell membrane → Na+/Glu/K+ * Na+/K+ pump is what moves molecules across membrane **Ineffective:** Freely crosses cell membrane → Urea (cannot create osmotic gradient) ## Footnote Retention incites H2O to cross membrane toward side w/ higher concentration of effective osmoles

Answer 2

responsible for maximizing the absorption of glucose from the intestinal tract and the recovery of glucose from the proximal tubule of the kidney following glomerular filtration | Facillitated diffusion *Glu follows Na+

Answer 3

--Na+ is exchanged for H+ (Na+ **IN** H+ **OUT**) → PCT --Utilized during metabolic acidosis ## Footnote PCT → CO2 + H2O = H2CO3 (carbonic acid) → HCO3 + H+ (**bicarb get reabsorbed in peritubule capillary** and **H+ gets excreted in distal convuluted tubule**

Answer 4

Obligated to follow Electrolytes --H2O obligated to follow Na+ -- Aldosterone responsible for reabsorbing obligated water

Answer 5

--HCO3 is exchanged for Cl-

Answer 6

--Thirst/AldosteroneADH main regulators --absorbed in PCT/ALOH via carrier protein --cotransport of Glu/AA --exchanged for H+/ammonium/K+ when reabsorbed

Answer 7

--Reabsorped in PCT/ALOH/DCT

Answer 8

--PCT H+ is sent out in exchanged for Na+ --DCT H+ →Alpha intercalated cells use ATP to pump H+ into urine --Ammonium combines with H+ in DCT to become a weak acid (keep urine pH from dropping too low)

Answer 9

homeostatic mechanism that uses the kidneys to help maintain the acid-base balance by excreting either an acidic or alkaline urine in response to changes in the hydrogen ion concentration of body fluids. Renal buffering involves a complex series of reactions within kidney tubules.

Answer 10

Measure - Calculated --does not exist just missing pieces of the equation! | If difference > 10 there is a problem

Answer 11

movement of water from a high concentration to a low concentration --membrane permeable to WATER not the SOLUTES | Na+ is KING of osmosis

Answer 12

formed by filtration of fluid out of microvessels and removed via the lymphatic system or transudation across the serosal surface of the organ

Answer 13

-- responsible for mediating the balance between microvascular filtration and the two interstitial outflows -- ↑= inhibits filtration and promotes lymph flow and serosal transudation -- interstitial fluid volume dependent on pressure and its relationship with the current volume

Answer 14

-- Endothelial glycocalyx is primarily the barrier to microvascular filtration -- COP of fluid on the interstitial side of the glycocalyx and w/i endothelial clefts has more direct effect on filtration than that of bulk interstitial fluid

Answer 15

glycoproteins, proteoglycans, and glycosaminoglycans that form a layer attached to the luminal surface of vascular endothelial cells

Answer 16

-- direction of microvascular filtration depends on the **sum of the hydrostatic and colloid osmotic pressure gradients** -- magnitude of filtration is the **product of the hydraulic conductivity, surface area, and net pressure gradient.**

Answer 17

-- consequence of the concentration of proteins, particularly albumin, as well as the redistribution of permeable ions induced by the presence of charges on those proteins

Answer 18

Removes interstitial fluid and returns it to the venous blood -- begins with terminal lymphatic vessels w/i interstitial space → larger vessels through lymph nodes, → terminates in the venous system --Pleural fluid and peritoneal fluid removed by lymphatic drainage to return to venous circulation

Answer 19

modified by numerous vasoactive mediators: prostaglandins thromboxane nitric oxide epinephrine acetylcholine substance P - neurotransmitter and a neuromodulator bradykinin - peptide that promotes inflammation

Answer 20

-- increased outflow pressure by increasing pumping activity via increases in the strength and frequency of contractions.

Answer 21

Edema-induced increases in **interstitial hydrostatic pressure will increase the rate of transudation** and may result in **effusion within the surrounding cavity of suspended organs**

Answer 22

intrinsic interdependent mechanisms include: (1) increased interstitial hydrostatic pressure (2) increased lymph flow (3) decreased interstitial colloid osmotic pressure (4) increased trans-serosal flow in organs within potential spaces ## Footnote they incur little energy cost and are effective because they respond rapidly to edema formation

Answer 23

1. **Venous hypertension** → Increased microvascular pressure and filtration 2. **Hypoproteinemia** → Decreased plasma colloid osmotic pressure, increased filtration 3. **Increased microvascular permeability** → Increased filtration 4. **Impaired lymph flow** →Vessel obstruction or damage 5. **Increased negativity of interstitial fluid pressure** → Shift in interstitial pressure–volume relationship, decreased interstitial pressure

Answer 24

**Hypothalamic osmoreceptors** sense changes in plasma osmolality, and changes of only 2–3 mOsm/L induce compensatory mechanisms to return the plasma osmolality to its hypothalamic setpoint -- two major physiologic mechanisms for controlling plasma osmolality are the antidiuretic hormone (ADH) system and thirst

Answer 25

ADH is a small peptide secreted by the posterior pituitary gland Stimulated by: -- elevated plasma osmolality -- decreased effective circulating volume.

Answer 26

Specialized group of cells in the **hypothalamus** -- with ↑ plasma osmolality = cell shrinkage → send impulses via neural afferents to the **posterior pituitary → stimulate ADH release**

Answer 27

When effective circulating volume is low, baroreceptor cells in the **aortic arch and carotid bodies** send neural impulses to the pituitary gland that stimulate ADH release -- H2o crosses into the hyperosmolar renal medullary interstitium and into the vasa recta along its osmotic gradient; the H2o is then returned to the general circulation

Answer 28

Aquaporins are channels that allow water to move from the tubular lumen into the renal tubular cell

Answer 29

When ADH activates the V2 receptor on the renal collecting tubular cell, aquaporin-2 molecules insert into the cell’s luminal membrane

Answer 30

become impermeable to water

Answer 31

Stimulate thirst -- The mechanisms by which hyperosmolality and hypovolemia stimulate thirst are similar to those that stimulate ADH release

Answer 32

RAAS = monitors and fine-tunes effective circulating volume ADH system maintains normal plasma osmolality

Answer 33

maintenance of effective circulating volume is prioritized over maintenance of normal plasma osmolality, so in patients with poor effective circulating volume, thirst and ADH release increase irrespective of plasma osmolality

Answer 34

increased water intake (from drinking) and water retention (from ADH action at the level of the kidney) decrease plasma [Na+] and can lead to hyponatremia (and thus hypoosmolality) in patients with poor effective circulating volume ## Footnote Ex: Chronic heart failure patient with hyponatremia

Answer 35

Plasma Na+ concentration independent from TB Na+ content TB Na+ content = total # of sodium molecules in the body, regardless of the ratio of sodium molecules to water molecules.

Answer 36

Na+ content determines the hydration status of the animal -- dehydrated, euhydrated, overhydrated

Answer 37

-- **increased total body sodium** -- increased quantity of fluid is maintained within the interstitial space and the animal appears overhydrated, regardless of the [Na+].

Answer 38

-- **decreased total body sodium content** --decreased quantity of fluid is maintained within the interstitial space and the animal appears dehydrated, regardless of the [Na+]. -- **hypovolemia occurs because fluid moves from IVS into the interstitial space** -- as a result of **decreased interstitial hydrostatic pressure = fluid deficit in the intravascular space**

Answer 39

1. Renal water loss 2. Osmotic diuresis due to glucosuria or mannitol causes an electrolyte-free water loss = hyperNa+ in sick animals with no water access 3. Diabetes insipidus (DI), a syndrome of inadequate release of or response to ADH 4. GI losses 5. Cathartic-containing Activate charcoal administration = pulls lyte-free H2O from ECS to GIT

Answer 40

DI pts depend on oral water intake to maintain normal plasma [Na+] because they cannot adequately reabsorb free water in the renal collecting duct -- become severely hypernatremic when they do not drink and hold down water

Answer 41

1. hypernatremic if denied access to water for extended periods 2. syndrome of hypodipsic hypernatremia has been reported in Miniature Schnauzers → due to impaired osmoreceptor or thirst center function.

Answer 42

Severe hypernatremia introduction of large quantities of sodium 1. hypertonic fluid administration (hypertonic saline, sodium bicarbonate) 2. sodium phosphate enemas 3. ingestion of seawater, beef jerky, or salt-flour dough mixtures. 4. Hyperaldosteronism can also cause hypernatremia due to excessive renal sodium retention

Answer 43

severe (usually >170 mEq/L) or occurs rapidly, -- -- Neurons intolerant of the cell volume change -- CNS signs such as obtundation, head pressing, seizures, coma, and death are the signs most commonly associated with clinical hypernatremia. ## Footnote Slow hyperNa+ typically asymptomatic

Answer 44

cells w/ Na+/K+-ATPase pumps lose volume (shrink) from hyperNa+ → water moves freely through the water-permeable cell membrane while these plentiful electrolytes do not --causes free water to move out of the relatively hypOosmolar ICS into hyperosmolar ECS = **decreased cell volume**. -- **brain has adaptive ways to protect against neuronal water loss**

Answer 45

-- neuronal water is lost to the hyperNa+ circulation, ↓ interstitial hydrostatic pressure draws fluid from CSF into the brain interstitium -- As plasma osmolality rises, Na+ and Cl- move rapidly from CSF into cerebral tissue → helps minimize brain volume loss by ↑ neuronal osmolality = drawing water back into the cells -- w/i 24hr, neurons begin to accumulate organic solutes to ↑ intracellular osmolality and help shift lost water back into the cell

Answer 46

molecules such as inositol and glutamate -- Generation and retention of these idiogenic osmoles begin within a few hours of neuron volume loss, though full compensation may take as long as 2–7 days

Answer 47

Hypernatremia should be treated even w/ no CS -- minor changes in [Na+] have been associated with poor outcome in people -- Patients with hyperNa+ have a water deficit = water should be replaced using fluid with a lower effective osmolality than the patient’s. -- [Na+] can be decreased by 0.5–1 mEq/L/hr in most situations of chronic or subacute hypernatremia without complication

Answer 48

Water may be supplemented intravenously (as 5% dextrose in water) or orally on an hourly schedule in animals that are alert, willing to drink, and not vomiting. ## Footnote Free water deficit calculation

Answer 49

water replacement must be more rapid Recent recommendation in people is to drop [Na+] in such cases by 2 mEq/L/hr until the [Na+] is high-normal

Answer 50

-- some authors recommend rapid infusion of 5% dextrose in water paired with hemodialysis to restore normal [Na+] as calculated using the water deficit equation -- When hemodialysis is not possible, aggressive water replacement over ≤12 hours seems reasonable

Answer 51

relatively safe, even in animals with cardiac or kidney disease, because the two-thirds of the infused volume that enters the cells cannot cause “fluid overload” or edema

Answer 52

CS 2nd, uncommon in critically ill dogs and cats because signs are not usually seen unless [Na+] is very low, usually <120 mEq/L -- Causes: 1. Decreased effective circulating volume 2. Hypoadrenocorticism 3. Renal tubular dysfunction: Diuretics, kidney failure 4. Syndrome of inappropriate antidiuretic hormone secretion

Answer 53

-- leads to ADH release and water intake in defense of intravascular volume = decreases [Na+]. -- CHF, Body cavity effusions, Edematous states → RAAS activation with increase water retention -- GI or Urinary Loss → compensatory drinking and retention

Answer 54

-- leads to hypoNa+ via decreased sodium retention (caused by hypoaldosteronism) combined with increased water drinking and retention in defense of inadequate circulating volume -- low circulating cortisol concentration leads to increased ADH release and resultant water retention regardless of intravascular volume status -- Animals w/ atypical hypoadrenocorticism, whose aldosterone production and release are normal, may also develop hyponatremia.

Answer 55

Loop or thiazide diuretic use causes hyponatremia by induction of hypovolemia, hypokalemia causing Na+ ions to shift **INTO** cells in **exchange** for K+ ions, and the inability to create dilute urine -- Kidney failure can cause hyponatremia by similar mechanisms.

Answer 56

Syndrome of inappropriate ADH secretion causes hyponatremia through water retention in response to improperly high circulating concentrations of ADH

Answer 57

cells w/ Na+/K+-ATPase pumps swell from hyponatremia b/c water moves into the relatively hyperosmolar cell from the hypoosmolar ECS -- **CNS signs consistent with cerebral edema**, such as obtundation, head pressing, seizures, coma, and ultimately death from brain herniation.

Answer 58

Interstitial and intracellular CNS edema increases intracranial tissue hydrostatic pressure -- pressure enhances fluid movement out of neurons and into the CSF, which flows out of the cranium, through the subarachnoid space and central canal of the spinal cord, and back into venous circulation -- Swollen neurons also expel solutes such as Na+/K+ and organic osmolytes to decrease intracellular osmolality and encourage water loss to the ECF, returning cell volume toward normal.

Answer 59

Complications of **HypoNa+ treatment** -- ODS is the result of **neuronal shrinking away from the myelin sheath as water moves out of the neuron during correction of hyponatremia.** -- myelinolysis commonly seen in thalamus -- CS usually manifest days after intervention, so the clinician cannot assume that a rapid change in plasma [Na+] has been well tolerated simply because no CNS signs are present during initial treatment. ## Footnote limb paresis, dysphagia, ataxia, and disorientation

Answer 60

Overzealous correction of severe hyponatremia has led to paresis, ataxia, dysphagia, obtundation, and other neurologic signs in dogs

Answer 61

-- hyponatremia caused by decreased effective circulating volume usually evolves over time -- Hyponatremia due to poor effective circulating volume usually self-corrects with improvement in perfusion, as ADH secretion drops and water is eliminated by the kidney -- Asymptomatic patients that are edematous may be treated with water restriction alone, and those that are asymptomatic and normally hydrated or dehydrated may be treated with administration of fluids with a sodium concentration that exceeds the patient’s [Na+].

Answer 62

chronic or the evolutionary timeline is unknown, the goal is to raise patient [Na+] by no more than **10 mEq/L during the first 24 hours** and by **no more than 8 mEq/L during each following 24-hour period,** not to exceed the low end of the reference interval some authors recommend an increase of **no more than 8 mEq/L over any 24-hour period,** particularly if risk for ODS is high due to severity or chronicity of the hyponatremia.

Answer 63

when correcting hyponatremia in animals being treated for concurrent hypokalemia → potassium supplementation will speed the correction of hyponatremia.

Answer 64

rapid water influx into neurons may exceed these cells’ ability to expel solute and water quickly enough -- Cerebral edema is treated with 7.0%–7.5% sodium chloride (hypertonic saline) at 3 to 5 ml/kg over 20 minutes.

Answer 65

hyponatremia in a patient with normal or elevated plasma osmolality -- most common cause in dogs and cats is hyperglycemia -- when **hyperglycemia is present, the excess glucose molecules cause an increase in ECF water, diluting sodium to a lower concentration.** -- other common cause is **mannitol infusion with retention (rather than renal excretion) of mannitol molecules**

Answer 66

For each 100 mg/dl increase in blood glucose, [Na+] drops by approximately 1.6–2.4 mEq/L.

Answer 67

Skeletal muscle cells

Answer 68

K+ concentration in intracellular space of dogs and cats is 140 mEq/L -- plasma space averages 4 mEq/L. -- Serum potassium levels therefore do not reflect whole body content or tissue concentrations.

Answer 69

pH regulation changes in osmolality insulin catecholamines aldosterone

Answer 70

Hyperosmolality causes the translocation of water from the cellular space, which drags cellular potassium into the extracellular fluid space

Answer 71

Insulin, catecholamines, and aldosterone transfer potassium from the extracellular space to the intracellular space.

Answer 72

Any increase in extracellular fluid potassium concentration triggers aldosterone release, which acts at the** distal renal tubules to increase Na-K-ATPase activity** -- promotes the transluminal transfer of potassium ions through the collecting duct principal cells into the renal tubular lumen, thus **allowing for potassium excretion and sodium reabsorption.**

Answer 73

responds to signals in the external environment and involves **sensors in the stomach and the hepatic portal regions** -- sensors detect local changes in potassium concentrations resulting from potassium ingestion and signal the kidney to alter potassium excretion to restore potassium balance -- **done without the influence of aldosterone.**

Answer 74

**(1) disorders of internal balance** Metabolic alkalosis Insulin administration Increased levels of catecholamines β-Adrenergic agonist therapy or intoxication Refeeding syndrome **(2) disorders of external balance** Renal potassium wasting Prolonged inadequate intake Diuretic drugs Osmotic or postobstructive diuresis Chronic liver disease Inadequate parenteral fluid supplementation Aldosterone-secreting tumor or any cause of hyperaldosteronism Prolonged vomiting associated with pyloric outflow obstruction Diabetic ketoacidosis Renal tubular acidosis Severe diarrhea Ingestion of barium-containing party sparklers glucocorticoid drugs Glucocorticoid drug administration

Answer 75

K+ necessary for **maintenance of normal resting membrane potential** -- neuromuscular abnormality induced by hypokalemia in dogs and cats is **skeletal muscle weakness from hyperpolarized (less excitable) myocyte plasma membranes** that may progress to hypopolarized membranes. -- ventroflexion or head neck, stiff gait, plantagrade stance

Answer 76

high intracellular/extracellular potassium concentration ratio induces a state of electrical hyperpolarization leading to prolongation of the action potential -- predisposes patient to atrial and ventricular tachyarrhythmias, atrioventricular dissociation, and ventricular fibrillation

Answer 77

Canine ECG abnormalities include **depression of the ST segment and prolongation of the QT interval** -- Increased P wave amplitude, prolongation of the PR interval, and widening of the QRS complex may also occur -- predisposes to digitalis-induced cardiac arrhythmias -- causes the **myocardium to become refractory to the effects of class I antiarrhythmic agents** (i.e., lidocaine, quinidine, and procainamide).

Answer 78

1. Intravenous potassium-containing fluids 1. Expired RBC transfusion 1. Drugs (potassium penicillin G, KCl, KPhos) 1. Translocation from ICF to ECF 1. Mineral acidosis (respiratory acidosis, NH4Cl, HCl, uremia) 1. Insulin deficiency 1. Acute tumor lysis syndrome 1. Extremity reperfusion following therapy for thromboembolism 1. Drugs (nonspecific β-blockers, cardiac glycosides) 1. Cardiopulmonary arrest

Answer 79

1. Anuric or oliguric renal injury 1. Urethral obstruction, bilateral ureteral obstruction 1. Uroabdomen 1. Hypoadrenocorticism 1. Gastrointestinal disease (trichuriasis, salmonellosis, perforated duodenum) 1. Chylothorax or pleural or peritoneal effusions 1. Drugs (ACE inhibitors, angiotensin receptor blockers, heparin, cyclosporine and tacrolimus, non-steroidal anti- inflammatory drugs, trimethoprim) 1. Pseudohyperkalemia 1. Thrombocytosis or leukocytosis (>1,000,000 platelets or >100,000 leukocytes) 1. Akita dog and other dogs of Japanese origin (secondary to in-vitro hemolysis) 1. Idiopathic 1. General anesthesia in healthy dogs (most notably Greyhounds)

Answer 80

-respiratory acidosis, uremia or pharmacologic induction by ammonium chloride, hydrogen chloride, or calcium chloride infusions -- causing potassium to move out of the intracellular space in exchange for hydrogen ions.

Answer 81

* insulin deficiency that results in a decreased cellular uptake of potassium * hyperosmolality that potentiates potassium translocation with water due to “solute drag” effect * decreased potassium excretion related to renal dysfunction (comorbidities, a prerenal component, or an acute kidney injury relative to hypovolemia/perfusion).

Answer 82

1. peaked, narrow T waves 1. prolonged QRS complex and interval 1. depressed ST segment 1. depressed P wave 1. atrial standstill 1. ventricular flutter/fibrillation

Answer 83

-- distal tubule is dependent on both adequate **glomerular filtration rate and urine flow to excrete potassium** -- severe reduction in both of these determinants with acute kidney injury significantly **impairs the ability of the distal tubule to excrete sufficient potassium**

Answer 84

In the absence of aldosterone, the resulting natriuresis causes a reduced effective circulating volume, which further impairs distal tubule potassium excretion.

Answer 85

Potassium can be released from increased numbers of circulating blood cells, especially platelets and leukocytes, causing an artifactual increase in potassium -- Akitas/japanese dogs

Answer 86

causes changes in **cardiac myocyte excitation and conduction** -- the concentration gradient across the cardiac cell membranes is reduced, **leading to a less negative resting membrane potential = makes cardiac cell membranes more excitable.** -- inactivates some of the Na+/K+ channels during the resting phase, making **these cells slower to reach threshold potential** -- **Acidemia results in extracellular shift in potassium as well as decreasing the β-adrenergic** receptors in cardiac tissues.

Answer 87

-- antagonize cardiotoxic effects of hyperK+ -- Increases threshold voltage but will not lower serum potassium

Answer 88

Causes metabolic alkalosis allowing for potassium to move intracellularly, paradoxical CNS acidosis with rapid administration

Answer 89

Allows for translocation of potassium into the intracellular space in the presence of endogenous insulin

Answer 90

Stimulates Na+/K+-ATPase to cause translocation of potassium into the cell

Answer 91

necessary for muscle contraction, neuromuscular function, and skeletal bone support

Answer 92

1. ionized (free), 1. protein bound 1. complexed (calcium bound to phosphate, bicarbonate, lactate, citrate, oxalate) Total calcium measures all 3

Answer 93

biologically active form in the body and is considered the most important indicator of functional calcium levels

Answer 94

complex process involving primarily parathyroid hormone (PTH), vitamin D metabolites, and calcitonin -- most of their effects seen on the intestine, kidney, and bone

Answer 95

synthesized and **secreted by the chief cells** of the parathyroid gland in response to hypocalcemia --normally inhibited by increased serum ionized calcium levels, as well as by increased concentrations of circulating calcitriol

Answer 96

through increased tubular reabsorption of calcium increased osteoclastic bone resorption increased production of calcitriol that then increases intestinal absorption of calcium

Answer 97

-- Cats and Dogs depend on Vit D in their diet -- cannot photosynthesize Vit D efficiently from their skin (like humans) -- After ingestion and uptake, vitamin D (**cholecalciferol**) is first hydroxylated in the liver and then it is **further hydroxylated to calcitriol** by the proximal tubular cells of the kidney -- **final hydroxylation** by the 1α-hydroxylase enzyme system to form **active calcitriol**

Answer 98

* Decreased levels of phosphorus, calcitriol, and calcium promote calcitriol synthesis * Increased levels of these substances all cause a decrease in calcitriol synthesis. * calcitriol primarily acts on the intestine, bone, kidney, and parathyroid gland

Answer 99

In the intestine, calcitriol enhances the absorption of calcium and phosphate at the level of the enterocyte

Answer 100

-- promotes bone formation and mineralization by regulation of proteins produced by osteoblasts -- also necessary for normal bone resorption because of its effect on osteoclast differentiation

Answer 101

calcitriol acts to inhibit the 1α-hydroxylase enzyme system, as well as **promote calcium and phosphorus reabsorption** from the glomerular filtrate

Answer 102

calcitriol acts genomically to inhibit the synthesis of PTH

Answer 103

**H**yperparathyroidism **A**ddison’s disease **R**enal failure Vitamin **D** toxicosis e.g. from rodenticides, house plants or psoriasis creams **I**diopathic (this is mainly a feline condition) **O**steolytic e.g. osteomyelitis **N**eoplasia e.g. lymphoma, anal sac adenocarcinoma **S**purious i.e. rule out lab error before starting investigation **G**ranulomatous disease ## Footnote diagnosis of hypercalcemia is confirmed with an ionized calcium measurement generally greater than 6 mg/dl or 1.5 mmol/L in the dog or greater than 5.7 mg/dl or 1.4 mmol/L in the cat.

Answer 104

-- polyuria and polydipsia (uncommon in cats), anorexia, constipation, lethargy, and weakness -- Severely affected animals may display ataxia, obtundation, listlessness, muscle twitching, seizures, or coma -- EKG abnormalities

Answer 105

**Bradycardia** may be detected on physical examination -- **prolonged PR interval**, widened QRS complex, shortened QT interval, shortened or absent ST segment, and a widened T wave.

Answer 106

specifically lymphoma, the most common cause in dogs

Answer 107

Rat bait containing cholecalciferol

Answer 108

Definitive treatment for hypercalcemia involves removing the underlying cause -- Acute therapy often involves the use of one or more of the following: intravenous fluids, diuretics (furosemide), glucocorticoids, and calcitonin

Answer 109

0.9% sodium chloride -- additional sodium ions provide competition for renal tubular calcium reabsorption, resulting in enhanced calciuria -- In addition, 0.9% sodium chloride is calcium-free, unlike other isotonic crystalloids

Answer 110

hypercalcemia can contribute to the development of hypertension secondary to vasoconstriction

Answer 111

enhances urinary calcium loss -- calciuresis

Answer 112

can cause a reduction in serum calcium concentration -- reduced bone resorption -- decreased intestinal calcium absorption -- increased renal calcium excretion

Answer 113

Calcitonin acts to decrease serum calcium concentrations mostly by **reducing the activity and formation of osteoclasts**

Answer 114

decreases the ionized and total calcium

Answer 115

**decrease osteoclastic activity**, thus **decreasing bone resorption** -- not considered drugs of choice for acute or crisis therapy -- can cause esophageal irritation and have been reported to cause abdominal discomfort, nausea, and vomiting in humans -- Bone toxicity from long-term treatment with bisphosphonates has been reported ## Footnote Pamidronate, zoledronate

Answer 116

Decreased total serum calcium is particularly common in those with **low circulating albumin status** -- common for **cats with pancreatitis** to have ionized hypocalcemia -- **Eclampsia in dogs**

Answer 117

1. Muscle tremors or fasciculations 1. Facial rubbing 1. Muscle cramping 1. Stiff gait 1. Behavioral change 1. Restlessness or excitation 1. Aggression 1. Hypersensitivity to stimuli 1. Disorientation 2. seizures 1. Panting 1. Pyrexia 1. Lethargy 1. Anorexia 1. Prolapse of third eyelid (cats) 1. Posterior lenticular cataracts 1. Tachycardia or ECG alterations (i.e., prolonged QT interval) **Uncommon:** 1. Polyuria or polydipsia 1. Hypotension 1. Respiratory arrest or death

Answer 118

Hypoalbuminemia Chronic renal failure Eclampsia Acute kidney injury Pancreatitis Soft tissue trauma or rhabdomyolysis Hypoparathyroidism Intestinal malabsorption, PLE, starvation ## Footnote theres like so many

Answer 119

-- **HyperMg++ and hypOMg++ can impair the secretion of PTH** and PTH actions on its receptor, so measurement of serum magnesium (preferably ionized magnesium) is important, especially in animals with **refractory hypocalcemia** -- treat the primary disease causing the disorder -- typically involves the administration of calcium salts, as well as vitamin D metabolites

Answer 120

severe ionized hypocalcemia can be life threatening because of myocardial failure and respiratory arrest tachycardia ECG alterations (i.e., prolonged QT interval) refractory hypotension respiratory arrest

Answer 121

less than 1% of total body magnesium is in the serum, serum magnesium concentrations do not always reflect total body magnesium stores -- normal serum magnesium concentration can occur when there is a total body magnesium deficiency. -- ionized, anion-complexed, and protein-bound fractions.

Answer 122

-- **second most abundant intracellular cation**, exceeded only by potassium Most of the magnesium is **found in bone and muscle.** **60%** of total body magnesium content is **present in bone.** **20% is in skeletal muscle** remainder is in other tissues, primarily the heart and liver

Answer 123

1. required for many metabolic functions 1. production and use of ATP 1. essential for protein and nucleic acid synthesis 1. regulation of vascular **smooth muscle tone** cellular second messenger systems 1. signal transduction

Answer 124

achieved through **intestinal absorption and renal excretion** -- Absorption occurs primarily in the small intestine **(jejunum and ileum)**

Answer 125

**LOH and DCT** are the main sites of magnesium reabsorption in the kidney -- **kidney is the main regulator** of serum magnesium concentration and total body magnesium content regulation is achieved by both glomerular filtration and tubular reabsorption

Answer 126

Increased concentrations of PTH, in addition to calcium concentration, most likely participate in magnesium conservation during lactation to supply the mammary glands with a sufficient amount

Answer 127

1. Decreased Intake 2. perioperative feline renal transplant recipients cats with diabetes mellitus and diabetic ketoacidosis 1. receiving peritoneal dialysis 2. dogs with congestive heart failure receiving furosemide therapy 1. protein-losing enteropathy 1. lactating dogs ## Footnote Magnesium losses can occur through the GI tract, kidneys, or both.

Answer 128

GIT: i**nflammatory bowel disease, malabsorptive or short-bowel syndromes, or other diseases that cause prolonged diarrhea.**

Answer 129

Acute renal dysfunction as a consequence of glomerulonephritis or the nonoliguric phase of acute tubular necrosis is often associated with a rise in the fractional excretion of magnesium

Answer 130

diuretic agents (furosemide, thiazides, mannitol) induce hypomagnesemia by increasing urinary excretion -- aminoglycosides, amphotericin B, cisplatin, and cyclosporine

Answer 131

changes in resting membrane potential, signal transduction, and smooth muscle tone -- effects of magnesium on the myocardium are linked to its role as a **regulator of other electrolytes, primarily calcium and potassium** -- cardiac arrhythmias, including atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, and ventricular fibrillation

Answer 132

-- **prolongs conduction through the atrioventricular node** -- prolongation of the PR interval, widening of the QRS complex, depression of the ST segment, and peaking of the T wave

Answer 133

**increases acetylcholine release from nerve terminals and enhances the excitability of nerve and muscle membranes** -- **increases the intracellular calcium content** in skeletal muscle -- **generalized muscle weakness, muscle fasciculations, ataxia, and seizures** -- **Esophageal or respiratory muscle weakness** can be manifested as dysphagia or dyspnea

Answer 134

hypokalemia that is refractory to aggressive potassium supplementation **may be due to magnesium deficiency causing excessive potassium loss through the kidneys**

Answer 135

**hypomagnesemia impairs PTH release and enhances calcium movement from extracellular fluid to bone** -- total and ionized hypocalcemia often accompanies magnesium depletion -- clinical signs of hypocalcemia seen with hypoMg++ possible

Answer 136

**Parenteral administration of magnesium sulfate may result in hypocalcemia because of chelation of calcium with sulfate** = magnesium chloride should be given if hypocalcemia is also present

Answer 137

-- hypotension, atrioventricular block, and bundle branch blocks -- usually are associated with intravenous boluses rather than CRIs

Answer 138

renal failure/kidney injury, endocrinopathies, and iatrogenic overdose, especially in patients with impaired renal function -- degree of hypermagnesemia parallels the degree of renal failure

Answer 139

-- lethargy, depression, and weakness -- Other clinical signs reflect the electrolyte’s action on the nervous and cardiovascular systems -- hyporeflexia = **decreased skeletal muscle response** -- **respiratory depression secondary to respiratory muscle paralysis in w/ profound elevation** -- **blockade of the autonomic nervous system**

Answer 140

-- prolongation of the PR interval and widening of the QRS complex due to delayed atrioventricular and interventricular conduction. -- Bradycardia -- severely high serum magnesium concentrations, complete heart block and asystole can occur

Answer 141

-- **Saline diuresis and furosemide** can also be used to accelerate renal magnesium excretion -- severe cases involving unresponsiveness **treated with intravenous calcium** -- **Calcium is a direct antagonist of magnesium at the neuromuscular junction** and may be beneficial in reversing the CVS effects of hypermagnesemia -- **anticholinesterase treatment** may be administered to offset the neurotoxic effects (Physostigmine)

Answer 142

-- body’s **major intracellular anion** -- essential for the production of ATP, guanosine triphosphate, cyclic adenosine monophosphate, and phosphocreatine, all of which function to **maintain cellular membrane integrity, energy** stores, metabolic processes, and biochemical messenger systems -- maintenance of **normal bone and teeth matrix** in the form of hydroxyapatite -- regulation of **tissue oxygenation** by way of 2,3-di-phosphoglycerate (**2,3-DPG**) -- support of cellular membrane structure -- buffering acidotic conditions

Answer 143

* 80% to 85% in the bone and teeth as inorganic hydroxyapatite * 14% to 15% in soft tissues * less than 1% in the extracellular space -- Phosphorus is present in the body as organic and inorganic phosphates -- **Organic phosphate is mostly intracellular** and **inorganic phosphate is mostly extracellular.**

Answer 144

Inorganic phosphate in the **form of 2,3-DPG accounts for 70% to 80% of phosphate in RBCs** -- Inorganic phosphate is further divided into orthophosphates and pyrophosphates -- most extracellular inorganic phosphate is in the form of orthophosphates

Answer 145

components of phospholipids, phosphoproteins, nucleic acids, enzymes, cofactors -- two-thirds of organic phosphate is in the form of phospholipids

Answer 146

blood chemistry analyzers only measure the **inorganic phosphates**

Answer 147

60% to 70% of ingested phosphate is **absorbed in small intestine** -- Serum phosphate balance is **dependent on GFR and tubular reabsorption in PCT** -- amount of phosphate reabsorbed is **dependent on dietary intake**

Answer 148

-- **(PTH) is a phosphaturic hormone** because it **decreases the tubular transport maximum for phosphate reabsorption** -- **Growth hormone, insulin**, insulin-like growth factor 1, and **thyroxine increase tubular phosphate reabsorption** -- **Growth hormone partially accounts for the expected hyperphosphatemia in young, growing animals**

Answer 149

**skeleton is the body’s phosphate reservoir** and provides a readily available source of phosphate **during periods of hypophosphatemia under the regulation of PTH and calcitonin**

Answer 150

1. Decreased Gastrointestinal Absorption 1. Transcellular Shifts 1. Increased Urinary Loss 1. Spurious or Laboratory Error

Answer 151

associated with: 1. alkalemia, 1. hyperventilation, 1. refeeding syndrome, 1. parenteral nutrition, 1. insulin administration, 1. glucose administration, 1. catecholamine administration or release, and salicylate toxicity

Answer 152

**Hypophosphatemia** is the **most common and critical electrolyte disturbance associated with refeeding syndrome. ** During chronic malnutrition, phosphate depletion can occur and may not be reflected by a decrease in serum phosphate concentration. Administration of enteral or parental nutrition to a patient with chronic malnutrition **stimulates insulin release, which promotes intracellular uptake of phosphate and glucose for glycolysis;** -- this transcellular shift may result in severe hypophosphatemia.

Answer 153

-- Insulin and glucose administration can cause severe hypophosphatemia in a patient with total body phosphate depletion -- stimulate glycolysis, promoting the synthesis of phosphorylated glucose compounds and intracellular shifts of phosphate.

Answer 154

severe hypophosphatemia and total body phosphate depletion **can result in widespread cellular dysfunction** -- **Hemolysis** can occur with severe hypophosphatemia because of decreased concentrations of red blood cell ATP and 2,3-DPG, spherocytosis -- **Decreased intracellular 2,3-DPG** = **impairs release of oxygen by hemoglobin to tissues**, = **tissue hypoxia** -- chemotaxis, phagocytosis, and bactericidal activity of leukocytes, which increases the risk of infection in critically ill animals ## Footnote O2/Hb CURVE

Answer 155

-- skeletal muscle changes include generalized weakness, tremors, and muscle pain -- Rhabdomyolysis (breakdown of muscle tissue) secondary to acute hypophosphatemia from refreeding syndrome -- **Neurologic signs** may include ataxia, seizures, and coma associated with **metabolic encephalopathy**

Answer 156

decreased renal excretion increased intake iatrogenic administration, and transcellular shifts -- decreased excretion are AKI, acute-on-chronic kidney disease, urethral obstruction, and uroabdomen

Answer 157

-- occur with **tumor lysis syndrome, rhabdomyolysis, and hemolysis** -- Tumor lysis syndrome is the clinical manifestation and laboratory sequelae of acute death of tumor cells that release potassium, phosphate, and nucleic acids into circulation and may cause AKI

Answer 158

syndrome of massive skeletal muscle tissue injury -- can cause hyperphosphatemia directly from **release of intracellular contents and indirectly by decreased renal excretion** from **resulting myoglobin-induced AKI** (although is rare in cats or dogs).

Answer 159

large doses of parenteral phosphate can cause not only hyperphosphatemia but **also hypomagnesemia, hypocalcemia, and hypotension** -- **Ingestion of cholecalciferol rodenticides and vitamin D3** skin creams (e.g., calcipotriene) can **rapidly increase serum phosphate concentration by increased intestinal absorption and release from bones**

Answer 160

**anorexia, nausea, vomiting, weakness, tetany, seizures, and dysrhythmias** -- Clinical manifestations of hyperphosphatemia **predominantly are due to hypocalcemia and ectopic soft tissue calcification**

Answer 161

Soft tissue calcium phosphate accumulation occurs when the calcium phosphate product is greater than 58 to 70 mg2/dl2 -- Tissues primarily affected by ectopic calcification include **cardiac, vasculature, renal tubules, pulmonary, articular, periarticular**, conjunctival, skeletal muscle, and skin

Answer 162

Arrhythmias: **polymorphic ventricular tachycardia or torsades de pointes** caused by prolongation of the QT interval, are **also associated with subsequent hypocalcemia and hypomagnesemia**

Answer 163

pH has a direct relationship with bicarbonate concentration and an inverse relationship with PCO2

Answer 164

1. regulation of PCO2 by alveolar ventilation (respiratory component) 1. buffering of acids by bicarbonate nonbicarbonate buffer systems (metabolic component) 1. changes in renal excretion of acid or base

Answer 165

uses pH, PCO2 and bicarbonate concentration for carbonic acid (H2CO3) -- pH is the consequence of the ratio of bicarbonate to PCO2.

Answer 166

Carbon dioxide acts as an acid in the body because of its ability to react with water to produce carbonic acid (H2CO3) -- increases in PCO2, the ratio of bicarbonate to PCO2 is decreased; hence pH falls.

Answer 167

CO2 + H2o ←→ H2CO3 ←→ H+ + HCO3- ## Footnote * increases in PCO2, the ratio of bicarbonate to PCO2 is decreased; hence pH falls. * with an increase in PCO2, the carbonic acid equation (below) will be driven to the right, increasing the hydrogen ion concentration

Answer 168

-- Elevations in bicarbonate concentration will drive the pH higher and represent a metabolic alkalosis while decreases in bicarbonate concentration represent a metabolic acidosis -- elevations in PCO2 will lead to elevations in bicarbonate while decreases in PCO2 will lead to a decrease in bicarbonate

Answer 169

defined as the **amount of strong acid or strong base** (in mmol/L) that **must be added** to 1 liter of fully oxygenated whole blood **to restore the pH to 7.4 ** -- **increased BE** (more positive value) is **consistent with a metabolic alkalosis** (either gain of bicarbonate or loss of acid) -- **decreased BE** (more negative value) **represents a metabolic acidosis**

Answer 170

-- advantage of using BE over bicarbonate concentration is that it is **independent of changes in the respiratory system** -- minimal changes in PCO2 present, the **BE and bicarbonate should correlate well** -- with substantial abnormalities in PCO2, the **BE is a more reliable measure of the metabolic component**

Answer 171

-- represents the metabolic acid-base component, not the respiratory system component -- measure of all the CO2 in a blood sample, and the majority of CO2 is carried as bicarbonate in the blood

Answer 172

-- Electroneutrality requires there to be an equal number of anions and cations in a physiologic system -- In reality there is no actual AG; the apparent AG exists because more cations in the system are readily measured than anions -- reflection of unmeasured ions

Answer 173

-- Bicarbonate concentration can fall with a rise in chloride concentration = **hyperchloremic metabolic acidosis** -- due to **disease processes causing bicarbonate loss in the gastrointestinal tract, or kidneys or can be iatrogenic,** secondary to administration of sodium chloride

Answer 174

occur from the **gain of acid** → excess acid in the system, **hydrogen ions will titrate (combine) with bicarbonate, leading to a fall in bicarbonate concentration** -- anion that accompanies the hydrogen ion (the conjugate base) will accumulate, maintaining electroneutrality and increasing the AG

Answer 175

High Anion Gap Metabolic Acidosis -- common causes of increased AG metabolic acidosis in small animals is DUEL -- AG can be calculated in an effort to help determine the underlying cause of the abnormality, assuming the patient is not hypoalbuminemic

Answer 176

**D**iabetic ketoacidosis **U**remic acids **E**thylene glycol toxicity **L**actic acidosis

Answer 177

* Renal bicarbonate loss * Gastrointestinal bicarbonate loss * Sodium chloride administration * Hypoadrenocorticism

Answer 178

Albumin and phosphorus -- states of hypoalbuminemia, abnormal unmeasured anions (e.g., **lactate or ketones**) may be present, but the calculated AG may remain within the reported normal range -- **AG is not reliable in hypoalbuminemic patients** -- Conversely, hyperalbuminemia will increase AG

Answer 179

-- abnormality in both the metabolic and respiratory components -- evident when both the respiratory and metabolic components have the same influence on acid-base balance (i.e., metabolic acidosis and respiratory acidosis or metabolic alkalosis and respiratory alkalosis) -- also present when there are abnormalities evident in both the metabolic and respiratory components, but the pH is in the normal range

Answer 180

-- results from an imbalance in CO2 production via metabolism and CO2 excretion via alveolar minute ventilation of the lung -- consequence of increased CO2 production or decreased alveolar ventilation -- diseases that **reduce respiratory rate, tidal volume, or both** -- Diseases that **prevent the transmission of impulses from the respiratory center to the respiratory muscles,** such as **cervical spinal cord disease, peripheral neuropathies** and diseases of the neuromuscular junction, can all cause respiratory paralysis and respiratory acidosis -- severe cases require MV

Answer 181

-- decreased PCO2 is the result of an increase in VA -- **disease processes that may stimulate an increased respiratory rate and/or tidal volume** -- include **significant hypoxemia, pulmonary parenchymal disease** (causing stimulation of **stretch receptors or nociceptors**), and airway inflammation -- central stimulation of respiratory rate and effort by the respiratory center → pathologic process resulting from brain injury, or it could be **behavioral as a result of pain or anxiety**.

Answer 182

most accurately determined by measurement of PaCO2. -- PvCO2 can be used to evaluate ventilation **if the animal is cardiovascularly stable**

Answer 183

Renal loss of bicarbonate from proximal or distal tubular dysfunction -- **proximal RTA,** there is **inadequate reabsorption of bicarbonate** in the proximal nephron -- **Distal RTA** is a disorder involving **inadequate hydrogen ion secretion** in the distal tubule that prevents maximal acidification of the urine pyelonephritis and IMHA | Fanconi syndrome - congenital dz ## Footnote Renal loss of bicarbonate can be an appropriate response to a persistent respiratory alkalosis (metabolic compensation)

Answer 184

-- Fluids containing a buffer such as lactated Ringer’s solution will aid in the metabolism of hydrogen ions -- hyperchloremic metabolic acidosis, use of lower chloride containing fluids (i.e., avoiding 0.9% NaCl) will also be of benefit. -- Treatment of metabolic acidosis due to an acid gain is primarily focused on the resolution of the underlying cause and appropriate selection of IV fluid therapy (DKA)

Answer 185

When the acidosis is severe or the compensatory respiratory alkalosis is considered detrimental to the patient, bicarbonate administration is indicated

Answer 186

Metabolic alkalosis can broadly be considered to occur due to either acid loss or bicarbonate gain -- Causes of acid loss include selective gastric acid loss such as can occur with gastrointestinal obstructive processes, excessive nasogastric tube suctioning -- Renal acid loss can occur due to loop diuretic administration, mineralocorticoid excess, and the presence of nonresorbable anions such as carbenicillins

Answer 187

Acid loss invariably occurs along with chloride in the gastrointestinal tract and renal system, and as a result, many animals with metabolic alkalosis will also be hypochloremic

Answer 188

Hypokalemia can play a significant role in the generation and maintenance of metabolic alkalosis. -- Intracellular shifts of hydrogen ions in exchange for potassium ions leaving the cells will increase the pH of the extracellular fluid. -- hypokalemia promotes renal acid loss -- **converse is true with acidemia**

Answer 189

-- cells exchange hydrogen ion for a potassium ion, using a special ion transporter located across the cell membrane. -- in order to help compensate for an acidosis, hydrogen ions enter cells and potassium ions leave the cells and enter the blood --In the acidotic patient there is a pseudo-hyperkalaemic state that may not reflect the total body potassium -- **Converse is true for alkalosis**

Answer 190

kidney has the ability to excrete large quantities of bicarbonate, such that metabolic alkalosis should be rectified rapidly. When metabolic alkalosis is persistent, there must be factors limiting renal bicarbonate excretion

Answer 191

Decreased effective circulating volume hypochloremia can both limit renal bicarbonate excretion. Hypokalemia and aldosterone excess further impair renal bicarbonate excretion

Answer 192

1. decreased myocardial contractility 1. arterial vasodilation 1. impaired coagulation 1. increased work of breathing secondary to carbon dioxide production 1. decreased renal and hepatic blood flow 1. insulin resistance 1. altered central nervous function

Answer 193

bicarbonate binds hydrogen ions (hence the alkalinizing effect) to form carbonic acid → this rapidly dissociates to CO2 and water -- If ventilation does not increase appropriately, an elevated PCO2 will cause a decrease in pH -- contraindicated in patients with evidence of hypoventilation

Answer 194

1. Increased hemoglobin affinity for oxygen 1. Increased blood lactate concentration 1. Paradoxical intracellular acidosis 1. Hypercapnia 1. Hypervolemia 1. Hyperosmolality 1. Hypernatremia 1. Hypocalcemia (ionized) 1. Hypomagnesemia (ionized) 1. Hypokalemia 1. Phlebitis

Answer 195

Bicarbonate cannot freely cross cell membranes, but the CO2 produced as bicarbonate is metabolized can freely enter cells -- Once intracellular, the CO2 combines with water leading to hydrogen ion release, causing intracellular acidosis -- evidence shows decreases in cellular and cerebrospinal fluid pH following bicarbonate therapy

Answer 196

1. partial pressure of carbon dioxide (PCO2) 1. the difference between strong cations and strong anions, known as the SID 1. total nonvolatile weak acids ## Footnote (sodium + potassium) − (chloride)

Answer 197

ions that are fully dissociated at physiologic pH -- major strong ions include sodium, potassium, calcium, magnesium, and chloride -- sodium and chloride are the most important strong ions in the body and SID is commonly simplified as the difference between serum sodium and chloride concentrations

Answer 198

due to hyponatremia, hyperchloremia, or a combination of the two -- may be best treated with an IV fluid with a higher SID, such as lactated Ringer’s with an effective SID of approximately 28 mmol/L (after the lactate is metabolized)

Answer 199

due to hypernatremia, hypochloremia, or both -- may benefit from a fluid with a low SID such as 0.9% saline (SID = 0)

Answer 200

Weak acids are only partially dissociated at physiologic pH. The major contributors to ATOT are albumin and phosphorus -- increases in ATOT = metabolic acidosis -- decreases in ATOT (primarily from decreased albumin) = metabolic alkalosis

Answer 201

evaluation of unmeasured anions in the SID approach and is similar to the use of anion gap (AG) -- if there are no unmeasured anions (SIG = 0) in the system -- unmeasured anions will cause a more positive value for SIG SIGsimplified = [albumin] × 4.9 – AG SIGsimplified = [albumin] × 7.4 − AG

Answer 202

free water effect on BE is due to changes in the water balance -- free water concentration is reflected by sodium concentration -- deficit of free water causing hypernatremia = positive FWE indicating an alkalinizing effect—a contraction alkalosis. -- excess of free water causing hyponatremia = negative FWE indicating an acidotic effect—a dilutional acidosis.

Answer 203

chloride and bicarbonate are reciprocally linked (i.e., when a chloride ion is excreted, a bicarbonate ion is retained and vice versa) -- gastric acid secretion, intestinal bicarbonate secretion, renal acid-base handling, and transcellular ion exchange -- Positive or negative effect

Answer 204

increased (positive) chloride effect (reflecting hypochloremia) is associated with a process that increases bicarbonate concentration and is indicative of an alkalinizing process

Answer 205

decreased chloride effect (negative) marks an acidotic process

Answer 206

Albumin acts as a weak acid and has many H+ binding sites -- Alkalizing effect = Hypoalbuminemia is equivalent to the removal of a weak acid from the system; it will be evident as a positive effect -- Acidifying effect = hyperalbuminemia will be evident as a negative effect, indicating an acidotic influence.

Answer 207

Phosphoric and sulfuric acids are products of protein metabolism and are normally excreted by the kidneys. -- AKI or failure retain these acids, resulting in a metabolic acidosis -- Elevated phosphorus will cause a negative effect and indicates an acidotic influence on BE -- hypophosphatemia does not cause a clinically significant alkalosis

Answer 208

-- produced from the conversion of pyruvate by lactate dehydrogenase, a reaction that consumes hydrogen ions -- Acidosis = accumulation of hydrogen ions from the hydrolysis of ATP -- In diseases where mitochondrial function is impaired, such as cellular hypoxia, there is accumulation of both lactate and hydrogen ions leading to lactic acidosis -- elevation = negative effect = acidic influence on BE

Answer 209

* Lactate is an intermediary metabolite of glucose oxidation that serves as a carbohydrate energy substrate reservoir. * it is produced in the cytosol and then either converted back to pyruvate to proceed through local aerobic cellular metabolism or exported out of the cell and transported to distant tissues in the bloodstream * all tissues are capable of producing lactate

Answer 210

Glycolysis is the cytosolic process (which occurs in the presence or absence of oxygen) by which **1 mole of glucose** is oxidized to **2 moles of pyruvate**, ATP, and reduced nicotinamide adenine dinucleotide (NADH) -- Glycolysis consumes NAD+ and produces NADH and pyruvate

Answer 211

With Glycolysis: normal aerobic conditions = only a small quantity of pyruvate is converted into lactate, catalyzed by lactate dehydrogenase (LDH) -- Ultimately lactate is either converted back into pyruvate in local or distant tissues and oxidized to produce energy or converted back into glucose by gluconeogenesis

Answer 212

WITH NORMAL O2 PRESENT = Pyruvate enters the mitochondria and is converted into acetyl CoA, the tricarboxylic acid (TCA) cycle, the electron transport chain, and oxidative phosphorylation to produce **36 moles of ATP**

Answer 213

To allow glycolysis to continue, NAD+ is replenished and pyruvate and H+ ions are removed by conversion of pyruvate to lactate -- only 2 moles of ATP per glucose molecule,

Answer 214

When the ATP made by glycolysis is utilized, H+ is released into the cytosol -- if oxygen supplies are insufficient, this cannot happen and H+ ions accumulate and are then transported out of the cell. -- acidosis from increased lactate production is mostly due to reduced H+ consumption, not increased lactate production per se.

Answer 215

each 1 mmol/L increase in lactate is associated with a concomitant reduction of the standardized base excess of 1 mmol/L.

Answer 216

Under conditions of health and aerobiosis, the liver and renal cortex are the predominant lactate-consuming organs -- Hepatic metabolism accounts for 30% to 60% of lactate consumption, and the liver is capable of metabolizing markedly increased lactate loads -- It is reabsorbed by the proximal convoluted tubule, and the renal threshold is 6 to 10 mmol/L.12-14

Answer 217

Whole blood lactate refers to the mean of intraerythrocytic and plasma lactate

Answer 218

**Increased Oxygen Demand:** * Exercise * Trembling/shivering * Muscle tremors * Seizure activity * Struggling **Decreased Oxygen Delivery:** * Systemic hypoperfusion * Local hypoperfusion * Severe anemia * Severe hypoxemia * Carbon monoxide poisoning

Answer 219

B1: **Associated with Underlying Disease** * Sepsis * Neoplasia * Diabetes mellitus * Liver disease * Thiamine deficiency * Pheochromocytoma * Hyperthyroidism * Alkalosis

Answer 220

B2: **Associated with Drugs or Toxins** * Acetaminophen * Activated charcoal * β2 agonists * Bicarbonate * Corticosteroids * Cyanide * Epinephrine * Ethanol * Ethylene gylcol * Glucose * Insulin * Lactulose * Methanol * Methylxanthines * Nitroprusside * Propofol * Propylene glycol * Salicylates * Strychnine * Sorbitol * TPN * Xylitol

Answer 221

B3: **Inborn Errors in Metabolism** * Mitochondrial myopathies * Enzymatic deficiencies * MELAS

Answer 222

-- Anemia-related hyperlactatemia is highly dependent on intravascular volume status and chronicity -- acute, severe, euvolemic anemia, hyperlactatemia does not develop until the packed cell volume (PCV) drops below 15%.

Answer 223

hypoxemia must also be very severe (partial pressure of oxygen [PaO2] 25 to 40 mm Hg) before pure hypoxemia-related hyperlactatemia develops

Answer 224

progressively worsening hypoperfusion shows a fairly linear relationship with plasma lactate concentration

Answer 225

Suggested mechanisms include stimulation of: skeletal muscle Na+/K+-ATPase by catecholamines mitochondrial dysfunction → direct cytochrome inhibition increased hepatic lactate production; reduced hepatic lactate extraction; impaired tissue oxygen extraction and capillary shunting

Answer 226

increased aerobic glycolysis secondary to adrenergic stimulation significantly contributes to sepsis-associated hyperlactatemia

Answer 227

Hyperlactatemia associated with neoplasia may be due to hypoperfusion in some cases, but malignant cells are known to exhibit atypical carbohydrate metabolism by preferentially utilizing glycolytic pathways for energy production despite sufficient oxygen availability (Warburg effect)

Answer 228

Epinephrine increases Na+/K+-ATPase activity and glycogenolysis resulting in hyperlactatemia -- conditions resulting in excess endogenous catecholamine release, such as pheochromocytoma, have also been associated with hyperlactatemia

Answer 229

Mitochondrial myopathies have been reported in the Jack Russell Terrier, German Shepherd, and Old English Sheepdog -- Pyruvate dehydrogenase deficiency has been recognized in the Clumber Spaniel and Sussex Spaniel

Answer 230

term cryptic shock has been used to describe ill or injured patients with high lactate concentrations without hypotension

Answer 231

D-Lactate is not detected by routine lactate analyzers and can only be measured by specialist laboratories -- Both D- and L-lactate are produced by some bacteria under anaerobic conditions -- In people, D-hyperlactatemia associated with short bowel syndrome and exocrine pancreatic disease is thought to contribute to encephalopathy

Answer 232

higher levels of muscle activity can significantly increase lactate (e.g., lots of struggling, trembling, tremors, marked exercise, and seizures).

Answer 233

Measurement of urine osmolality and electrolyte concentration can provide valuable insight regarding water balance, effective circulating volume (ECV), and electrolyte and acid-base disorders -- may provide insight into renal handling of water and electrolytes for patients with disturbances in extracellular fluid volume or content -- may be helpful in determining the nature of a patient’s polyuria and evaluating specific serum electrolyte abnormalities -- determining cause for hypoNa+

Answer 234

Assessment of ECV < 20, Decreased ECV (Na avid) Aldosterone presence

Answer 235

Assessment of ECV Assessment of metabolic alkalosis < 15–25 = Chloride responsive metabolic alkalosis >15–25 = Chloride unresponsive metabolic alkalosis

Answer 236

Assessment of Hypokalemia < 15–20 = Nonrenal K loss >40 = Renal K wasting Hyperkalemia >40 = Nonrenal cause (e.g., hypoadrenocorticism)

Answer 237

Assessment of solute free water excretion Positive = Free water excretion (absence of ADH secretion and/or response) Negative = Free water retention (ADH secretion and response)

Answer 238

-- continuously in flux because it is being lost through evaporation, elimination, and metabolic processes and gained from food and water intake -- volume and distribution of TBW are under the control of hormonal mechanisms that maintain water and sodium balance by regulating renal water and salt excretion and reabsorption, whereas thirst mechanisms influence water intake

Answer 239

Loss of fluid with little or no solute (i.e., hypotonic fluid loss) will increase plasma solutes per kilogram water (osmolality). -- increase in the plasma osmolality is detected by the **supraoptic** and **paraventricular** nuclei in the hypothalamus = release of antidiuretic hormone (ADH; arginine vasopressin),

Answer 240

Hypovolemia stimulates baroreceptors that cause the hypothalamic-pituitary-adrenal axis to produce and release ADH, aldosterone, renin, and cortisol = renal water/Na+ conservation

Answer 241

overexpansion of the cardiovascular system causes stretch of the atria and release of atrial natriuretic peptide = increase in renal water/Na+ excretion

Answer 242

Ninety percent of acute changes in body mass can be attributed to a change in TBW -- 1 kg change in TBW may be equivalent to 1 L change in TBW

Answer 243

examining mucous membrane moisture, skin tent response, eye position, and corneal moisture -- minimum degree of interstitial dehydration that can be detected in the average patient is approximately 5% of body weight -- greater than 12% is likely to be fatal

Answer 244

Tacky mucous membranes ± some change in skin turgor

Answer 245

Mild decreased skin turgor Dry mucous membranes

Answer 246

Obvious decreased skin turgor Retracted globes within orbits

Answer 247

Persistent skin tent due to complete loss of skin elasticity Dull corneas Evidence of hypovolemia

Answer 248

increased turgor of the skin and subcutaneous tissue, giving it a gelatinous character; peripheral or ventral pitting edema can also occur. Chemosis and clear nasal discharge may also be evident

Answer 249

-- assessed through the examination of perfusion parameters (MM color, capillary refill time, heart rate, and pulse quality) and determination of jugular venous distensibility -- rapid intravascular losses such as hemorrhage can cause hypovolemia without causing clinically detectable changes in the interstitial fluid compartment

Answer 250

cannot be identified on physical examination -- rely on changes in the effective osmolality of ECF (primarily changes in sodium concentration) to mark changes in cell volume -- With decreases in ECF effective osmolality = movement of water into the ICF compartment = increase in intracellular volume -- increases in ECF effective osmolality = decreases in intracellular volume

Answer 251

TBW loss is due to loss of a fluid with little or no salt content (i.e., hypotonic fluid loss) = increases in ECF osmolality, reflected by increases in serum sodium concentration -- water will move from the ICF compartment to the ECF compartment -- loss of ICF volume has the greatest impact on the central nervous system, and if the degree of solute-free water loss is severe and acute it can result in neurologic abnormalities and possibly death as a result of neuronal cell shrinkage ## Footnote Ex: uncontrolled diabetes insipidus

Answer 252

net loss or gain of fluid with a salt concentration similar to that of the ECF = changes in the ECF volume with little change in ECF osmolality = no change in the ICF volume -- will lead to interstitial dehydration/overhydration -- minimal change in serum sodium concentration with isotonic fluid gain or loss

Answer 253

Urine osmolality and USG will increase as water is reabsorbed from the urine filtrate in states of ECF dehydration -- decrease as water is excreted from the urine in states of ECF over hydration. -- will be limited if the patient has received IV fluid therapy or diuretic administration before urinalysis

Answer 254

resuscitation, optimization, stabilization, and evacuation

Answer 255

For example, the caudal vena cava (CVC) diameter and left atrial to aortic root ratio (LA:Ao) are static markers, while the CVC collapsibility index is a dynamic marker (see below)

Answer 256

-- mini-boluses of isotonic crystalloids as low as 3–5 ml/kg, administered within 5 minutes -- PLR shifts the volume from the venous system of the legs to the central circulation, mimicking the effect of a fluid bolus. -- may elicit an adrenergic/sympathetic or white coat response in awake companion animals

Answer 257

right atrial pressure (RAP), and the resistance to venous flow (Rv) are the main driving forces of venous return and can be expressed through the following formula: venous return = (MSFP – RAP/Rv) --other words, venous return can be increased by one of three mechanisms: (1) lowering RAP, (2) decreasing Rv, and (3) increasing MSFP

Answer 258

accuracy of chest radiographs to detect signs of hypo- or hypervolemia through changes in cardiac size, CVC, and pulmonary vessel diameter has been reported at 44% in humans

Answer 259

assessed indirectly through upstream and downstream measures of perfusion (e.g., arterial blood pressure and lactate, respectively)

Answer 260

dogs with clinical signs of hypovolemia have smaller left ventricular and left atrial lumen sizes, and thicker left ventricular walls -- proportional to the severity of hypovolemia -- increased ventricular wall size, and decreased ventricular and atrial lumen size has been observed in cats following volume depletion (7%–10% body weight), while volume administration results in increasing left atrial and ventricular lumen size

Answer 261

(A) will increase preload following a fluid bolus, without a significant increase in extravascular lung water (EVLW). As preload increases, stroke volume (SV) will also increase until the optimal preload is achieved. A fluid nonresponsive patient (B) will have a marginal to no increase in preload, and thus no improvement in SV, but a significant increase in EVLW

Answer 262

Superimposition of the Frank–Starling and Marik–Phillips curves demonstrating the effects of increasing preload on stroke volume (SV) and lung water in a patient who is preload responsive (a) nonresponsive (b). With sepsis, the extravascular lung water (EVLW) curve is shifted to the left. CO; cardiac output, CVP; central venous pressure

Answer 263

hydrostatic and colloid osmotic pressure [COP] in the intraluminal and extraluminal spaces) -- govern the magnitude of fluid filtration from the capillary into the interstitial compartment.

Answer 264

plasma albumin accounts for 80% of plasma COP

Answer 265

fluids containing small solutes with molecular weights less than 500 g/mole --readily crosses capillary endothelium and equilibrate throughout the ECF compartment. -- lag time of 20 to 30 minutes for electrolytes to distribute evenly in the extracellular fluid compartments

Answer 266

5% dextrose in water is considered free water because after dextrose metabolism it does not contain an effective osmole.

Answer 267

Less than one-third of the volume of crystalloids administered remains in the intravascular space 30 minutes after administration.

Answer 268

lower the fluid tonicity, the greater the dilutional effect on extracellular fluid tonicity, resulting in an osmotic gradient favoring free water movement into the intracellular space and leaving less of the administered fluid volume in the extracellular space.

Answer 269

range of 270 to 310 mOsm/L -- do not cause significant fluid shifts between intracellular and extracellular fluid compartments in normal animals

Answer 270

0.45% saline has an osmolarity of 154 mOsm/L with a sodium [and chloride] concentration of 77 mEq/L each 5% dextrose in free water is a unique isoosmotic solution (252 mOsm/L) with hypotonic effects since dextrose is rapidly metabolized and free water remains (osmolarity of 0 mOsm/L). ## Footnote Sterile water with an osmolarity of 0 mOsm/L

Answer 271

should never be administered directly intravenously because of the risk of intravascular hemolysis and endothelial damage

Answer 272

Hypotonic fluids replenish free water deficits and are useful for treating animals with hypernatremia secondary to hypotonic fluid loss -- distribute throughout both intracellular and extracellular fluid compartments, with less remaining extracellularly in comparison to isotonic fluids

Answer 273

-- rapid IV administration of hypotonic fluids drops plasma and ECF osmolarity (mainly determined by sodium level) quickly; consequently, water shifts from the ECF space to the intracellular space -- may also lead to life-threatening cerebral edema

Answer 274

7.2% HTS = 2566 mOsm/L

Answer 275

-- causes a free water shift (i.e., osmosis) from the intracellular space to the extracellular space, expanding the extracellular fluid volume by 3 to 5 times the volume administered -- Osmotic fluid shifts from the interstitial space into the intravascular space start immediately after intravenous administration of hypertonic solution -- Free water from the intracellular fluid compartment then moves into the extracellular fluid compartment as the interstitial fluid osmolarity rises

Answer 276

hypovolemic shock, intracranial hypertension, and severe hyponatremia -- It transiently improves CO and tissue perfusion via arteriolar vasodilation (decreased afterload), volume loading (increased preload), and reduced endothelial swelling, and has a weak positive inotropic effect -- improves cerebral perfusion pressure in head trauma patients by augmenting mean arterial blood pressure and decreasing ICP

Answer 277

intravascular volume expansion effect of hypertonic saline is transient (< 30 minutes) because of the redistribution of electrolytes throughout the extravascular space and osmotic diuresis

Answer 278

rates cannot exceed 1 ml/kg/min because hypotension may result from central vasomotor center inhibition or peripheral vasomotor effects mediated by the acute hyperosmolarity (bradycardia and vasodilation).

Answer 279

acid-base effects of crystalloid administration depend largely on the buffer content of the fluid -- Acetate and lactate are weak buffers included in some crystalloids such as Normosol-R, LRS, and Plasma-Lyte -- Metabolism of these buffers consumes hydrogen ions, resulting in an alkalinizing effect -- beneficial when treating patients with a metabolic acidosis

Answer 280

Colloid solutions contain large hydrophilic molecules (>10,000 Da) that do not readily cross the vascular endothelium and remain within the intravascular space in patients with an uncompromised, intact vascular barrier

Answer 281

Includes endothelial glycocalyx layer, the endothelial basement membrane, and the extracellular matrix to the tradition principle -- subglycocalyx COP replaces the interstitial fluid COP as a determinant of transendothelial flow

Answer 282

describes how an increased intravascular to interstitial hydrostatic pressure gradient leads to transvascular fluid flux into the interstitial space at the arteriolar end of the capillary; fluid is subsequently reabsorbed into the intravascular space at venous end of the capillary due to an increased intravascular COP ## Footnote subglycocalyx COP replaces the interstitial fluid COP as a determinant of transendothelial flow in revised equation

Answer 283

albumin, globulins, and fibrinogen

Answer 284

major use of HES solutions is to rapidly expand the intravascular volume with small volume resuscitation by increasing the COP -- HES is synthesized from amylopectin, which is a naturally occurring starch, derived from either potatoes or corn, and is hydroxylated to prevent rapid degradation by α-amylase

Answer 285

fresh frozen plasma (FFP), frozen plasma, cryopoor plasma (CPP), cryoprecipitate (CRYO), human serum albumin (HSA), canine albumin, and intravenous immunoglobulin

Answer 286

should not be used in conjunction with calcium supplementation. Overzealous phosphate administration can result in iatrogenic hypocalcemia and associated neuromuscular signs, hypernatremia, hypotension, and diffuse tissue calcification

Answer 287

1. paradoxical cerebral acidosis, 1. increased carbon dioxide production and the potential for hypercapnia, 1. increased sodium and osmole concentration, risk for circulatory system overload, 1. iatrogenic metabolic alkalosis, 1. changes to the oxygen dissociation curve (Bohr effect), 1. hypokalemia

Answer 288

vital to achieve metabolic breakdown of the remaining ketone bodies and resolve acidosis

Answer 289

a shortage of glucose in the brain thereby affecting the function of neurons and altering brain function and behavior. Other subtler signs may include pupil dilation, anxiety, or drooling

Answer 290

characterized by hyperglycemia (blood glucose >600 mg/dL), hyperosmolarity (>350 mOsm/L), and dehydration without the presence of ketoacidosis ## Footnote normal osmolarity in dogs is approximately 290–310 mOsm/L and 290–330 mOsm/L in the cat.

Answer 291

Sodium concentration should be reduced at a rate no greater than 0.5 mEq/L/h to avoid cerebral edema and worsening of neurological status